High-Mechanical Index (MI) Flash Imaging during Late Phase of Contrast-enhanced Ultrasound (CEUS): A Novel Approach to Enhance Differential Diagnosis of Malignant and Benign Focal Liver Lesions (FLLs)

Background and aim: Although contrast-enhanced ultrasound (CEUS) is highly accurate, approximately 20% of focal liver lesions (FLLs) remain inconclusive. High-Mechanical Index (MI) flash imaging in the late phase of CEUS provides diagnostic information, yet its value is unexplored. We therefore conducted a prospective study to assess its feasibility and performance for differentiating malignant from benign FLLs. Methods: From January 2024 to April 2025, 155 consecutive patients with a single FLL underwent CEUS (MI: 0.12) followed by high-MI flash imaging (MI: 1.2). Hypo-echogenicity on flash imaging was served as the diagnostic criterion for malignant FLLs. Technical successful rate, observer agreement and diagnostic performance of flash imaging were assessed. The clinical value of flash imaging was determined in CEUS-inconclusive cases. Results: Flash imaging was technically successful in 143 (92.3%) FLLs (102 malignant; 41 benign). Hypo-echogenicity was present in 96.1% (98/102) malignant versus 34.1% (14/41) benign FLLs on flash imaging ( p < 0.001). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of flash imaging were 96.1%, 65.9%, 87.5%, 87.1%, and 87.4%, respectively. Inter- and intra-observer agreement were both excellent (inter: 92.3%; intra: 93.0 and 93.7%). Flash imaging achieved 80.0% differential diagnostic accuracy in CEUS-inconclusive cases. When CEUS and flash imaging were integrated, the overall differential diagnostic accuracy increased from 82.5% to 97.9% ( p < 0.001). Conclusion: High-MI flash imaging during late phase of CEUS demonstrates high technical success, excellent reproducibility and significant discriminative ability for FLLs, especially enhancing the discriminative ability of CEUS in CEUS-inconclusive cases.